Variant 1-15518120-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001229.5(CASP9):c.408T>C(p.Phe136Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,613,430 control chromosomes in the GnomAD database, including 236,280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.59 ( 26847 hom., cov: 32)

Exomes 𝑓: 0.53 ( 209433 hom. )

Consequence

CASP9
NM_001229.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.325

Variant links:

Genes affected

CASP9 (HGNC:1511): (caspase 9) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein can undergo autoproteolytic processing and activation by the apoptosome, a protein complex of cytochrome c and the apoptotic peptidase activating factor 1; this step is thought to be one of the earliest in the caspase activation cascade. This protein is thought to play a central role in apoptosis and to be a tumor suppressor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

CASP9 links:

CASP9 (HGNC:):

CASP9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 1-15518120-A-G is Benign according to our data. Variant chr1-15518120-A-G is described in ClinVar as [Benign]. Clinvar id is 3058888.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.325 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP9	NM_001229.5 linkuse as main transcript	c.408T>C	p.Phe136Phe	synonymous_variant	2/9	ENST00000333868.10	NP_001220.2	P55211-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP9	ENST00000333868.10 linkuse as main transcript	c.408T>C	p.Phe136Phe	synonymous_variant	2/9	1	NM_001229.5	ENSP00000330237.5		P55211-1

Frequencies

GnomAD3 genomes

AF:

0.587

AC:

89138

AN:

151956

Hom.:

26808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.705

Gnomad AMI

AF:

0.512

Gnomad AMR

AF:

0.498

Gnomad ASJ

AF:

0.499

Gnomad EAS

AF:

0.647

Gnomad SAS

AF:

0.426

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.538

Gnomad OTH

AF:

0.556

GnomAD3 exomes

AF:

0.532

AC:

133590

AN:

251268

Hom.:

36678

AF XY:

0.526

AC XY:

71487

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.701

Gnomad AMR exome

AF:

0.410

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.648

Gnomad SAS exome

AF:

0.431

Gnomad FIN exome

AF:

0.645

Gnomad NFE exome

AF:

0.535

Gnomad OTH exome

AF:

0.522

GnomAD4 exome

AF:

0.532

AC:

777148

AN:

1461358

Hom.:

209433

Cov.:

AF XY:

0.529

AC XY:

384670

AN XY:

726904

show subpopulations

Gnomad4 AFR exome

AF:

0.704

Gnomad4 AMR exome

AF:

0.419

Gnomad4 ASJ exome

AF:

0.499

Gnomad4 EAS exome

AF:

0.645

Gnomad4 SAS exome

AF:

0.432

Gnomad4 FIN exome

AF:

0.638

Gnomad4 NFE exome

AF:

0.530

Gnomad4 OTH exome

AF:

0.539

GnomAD4 genome

AF:

0.587

AC:

89222

AN:

152072

Hom.:

26847

Cov.:

AF XY:

0.587

AC XY:

43652

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.705

Gnomad4 AMR

AF:

0.498

Gnomad4 ASJ

AF:

0.499

Gnomad4 EAS

AF:

0.646

Gnomad4 SAS

AF:

0.425

Gnomad4 FIN

AF:

0.652

Gnomad4 NFE

AF:

0.538

Gnomad4 OTH

AF:

0.552

Alfa

AF:

0.529

Hom.:

19463

Bravo

AF:

0.581

Asia WGS

AF:

0.553

AC:

1923

AN:

3478

EpiCase

AF:

0.520

EpiControl

AF:

0.516

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CASP9-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.4

DANN

Benign

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over